Pharmacokinetics of lopinavir in HIV type-1-infected children taking the new tablet formulation once daily

Antivir Ther. 2008;13(8):1087-90.

Abstract

Background: Recently, a new tablet formulation of the widely used HIV protease inhibitor lopinavir/ritonavir was licensed. Here, we present a pilot study of the pharmacokinetics of the new adult tablet formulation taken once daily in children.

Methods: Lopinavir pharmacokinetics of the new adult tablet formulation were evaluated in 15 HIV type-1-infected children between 4 and 15 years of age. A target dose of 460/115 mg/m2 was administered once daily. Plasma concentrations of lopinavir over the course of 24 h were determined with a validated HPLC method.

Results: The median lopinavir dose was 498 mg/m2 (range 424-548). The mean +/- SD for lopinavir area under the 24 h curve was 217.9 +/- 44.9 mg/l x h, the maximum concentration was 14.8 +/- 2.4 mg/l and the concentration 24 h after intake was 3.1 +/- 2.6 mg/l. The half-life of lopinavir was 5.8 +/- 4.5 h and the median time to maximum concentration was 5.8 h (range 1.8-12.2). Overall, the tablet formulation resulted in greater exposure to lopinavir with less variability compared with the soft-gel capsule formulation. All children treated with the new adult tablet formulation had undetectable viral loads (< 50 copies/ml) during 24 weeks follow-up.

Conclusions: The tablet formulation could probably result in improved lopinavir dosing and increases the feasibility of once-daily lopinavir/ritonavir-based regimens in children.

MeSH terms

  • Adolescent
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Area Under Curve
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / classification
  • Half-Life
  • Humans
  • Lopinavir
  • Male
  • Pyrimidinones / administration & dosage*
  • Pyrimidinones / blood
  • Pyrimidinones / pharmacokinetics*
  • Pyrimidinones / therapeutic use
  • Tablets

Substances

  • Anti-HIV Agents
  • Pyrimidinones
  • Tablets
  • Lopinavir